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Overactivation of the NF-κB pathway impairs molar enamel formation

Item Type:Article
Title:Overactivation of the NF-κB pathway impairs molar enamel formation
Creators Name:Yamada, A. and Kawasaki, M. and Miake, Y. and Yamada, Y. and Blackburn, J. and Kawasaki, K. and Trakanant, S. and Nagai, T. and Nihara, J. and Kudo, T. and Meguro, F. and Schmidt-Ullrich, R. and Liu, B. and Hu, Y. and Page, A. and Ramírez, Á. and Sharpe, P.T. and Maeda, T. and Takagi, R. and Ohazama, A.
Abstract:OBJECTIVE: Hypohidrotic ectodermal dysplasia (HED) is a hereditary disorder characterized by abnormal structures and functions of the ectoderm-derived organs, including teeth. HED patients exhibit a variety of dental symptoms, such as hypodontia. Although disruption of the EDA/EDAR/EDARADD/NF-κB pathway is known to be responsible for HED, it remains unclear whether this pathway is involved in the process of enamel formation. EXPERIMENTAL SUBJECTS AND METHODS: To address this question, we examined the mice overexpressing Ikkβ (an essential component required for the activation of NF-κB pathway) under the keratin 5 promoter (K5-Ikkβ). RESULTS: Upregulation of the NF-κB pathway was confirmed in the ameloblasts of K5-Ikkβ mice. Premature abrasion was observed in the molars of K5-Ikkβ mice, which was accompanied by less mineralized enamel. However, no significant changes were observed in the enamel thickness and the pattern of enamel rods in K5-Ikkβ mice. Klk4 expression was significantly upregulated in the ameloblasts of K5-Ikkβ mice at the maturation stage, and the expression of its substrate, amelogenin, was remarkably reduced. This suggests that abnormal enamel observed in K5-Ikkβ mice was likely due to the compromised degradation of enamel protein at the maturation stage. CONCLUSION: Therefore, we could conclude that the overactivation of the NF-κB pathway impairs the process of amelogenesis.
Keywords:Molar, Enamel, NF-κB, Tooth Development, Animals, Mice
Source:Oral Diseases
Date:5 May 2020
Official Publication:https://doi.org/10.1111/odi.13384
PubMed:View item in PubMed

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